The general goal of the proposed research is an evaluation of the effect naturally occurring vasoactive agents have on resistance to blood flow through skeletal muscle. The method of study will allow for examination of interaction and interrelationships among these and not just the effect of single agents. Once the local effects of these interactions are determined, their effectiveness in completing with neurogenic vasoconstrictor mechanisms will be evaluated. As such, this will allow for an examination of the interactions that exist between local factors and autonomic mechanisms. This type of approach will offer multiple opportunities for experimental manipulation. While the vascular bed of skeletal muscle will serve as a model for experimental design, the approach will be extended to histologically dissimilar tissues such as subcutaneous adipose tissue, salivary gland, cutaneous bed, etc. By using a standard preparation and procedure comparison of data from study to study will be facilitated which will assistin determining similarities and differences in blood flow control mechanisms for different types of tissues. Using this information as a base, these studies are being extended to examine reflex effects in these different tissues induced by events that stimulate clinical states, e.g., myocardial ischemia, systemic and pulmonary hyperosmolality, lung hyperinflation ad hypoxemia. An examination of the effects of stimulation of specific CNS structures (e.g., posterior hypothalamus) on blood flow in these histologically disimilar structures is in progress.